Cytotoxicity of adenoviruses expressing the wild-type p53 gene to esophageal carcinoma cells is linked with the CAR expression level and indirectly with the endogenous p53 status
Cytotoxicity of adenoviruses expressing the wild-type p53 gene to esophageal carcinoma cells is linked with the CAR expression level and indirectly with the endogenous p53 status
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DOI：
10.1038/cgt.2009.21
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发表时间：
2009-11-01
影响因子：
6.4
通讯作者：
Tagawa, M.
中科院分区：
文献类型：
--
作者：
Ma, G.;Kawamura, K.;Tagawa, M.
我们研究了表达p53基因（Ad-p53）的腺病毒（Ad）在9个人食管癌细胞系中的细胞毒性效应，与Ad受体表达和内源性p53基因状态有关。Ad-p53介导的细胞毒性与柯萨奇病毒腺病毒受体（CAR）的表达水平有关，但与CD 51的表达水平无关，两者都是5型Ad受体。与早期的研究相反，我们发现野生型p53基因的肿瘤细胞的细胞毒性大于突变型p53基因的肿瘤细胞。然而，E1 B55 kDa分子缺陷型Ad（Ad-delE 1B 55）的细胞毒活性与CAR表达水平或内源性p53状态无关。我们注意到，具有野生型p53基因的肿瘤细胞显示出更高的CAR表达水平，尽管用Ad-p53转导并没有上调突变细胞中的CAR表达。我们还检测了Ad-53介导的两种配对成纤维细胞（亲本和永生化的p53功能丧失的成纤维细胞）中的细胞毒性，并且表明CAR表达水平比内源性p53状态在细胞毒性中更有影响。这些数据表明，CAR表达水平比内源性p53状态更能预测Ad-p53介导的食管癌细胞毒性。Cancer Gene Therapy（2009）16，832-840; doi：10.1038/cgt.2009.21; 2009年4月10日在线发表
We examined cytotoxic effects of adenoviruses (Ad) expressing the p53 gene (Ad-p53) in nine human esophageal carcinoma cell lines with respect to the Ad receptor expression and the endogenous p53 gene status. Ad-p53-mediated cytotoxicity was related with an expression level of the coxsackievirus adenovirus receptor (CAR) but not with that of CD51, both of which are type 5 Ad receptors. Contrary to earlier studies, we found that the cytotoxicity was greater in tumor cells with the wild-type p53 gene than in those with mutated p53. The cytotoxic activity of Ad defective of E1B55kDa molecules (Ad-delE1B55), however, was not linked with the CAR expression level or the endogenous p53 status. We noticed that the tumor cells with the wild-type p53 gene showed greater CAR expression levels, although transduction with Ad-p53 did not upregulate the CAR expression in the mutated cells. We also examined the Ad-53-mediated cytotoxicity in two kinds of paired fibroblasts, parent and immortalized with loss of the p53 functions, and showed that the CAR expression level was more influential than the endogenous p53 status in the cytotoxicity. These data suggest that CAR expression level is a better predictive marker than endogenous p53 status for Ad-p53-mediated cytotoxicity in esophageal carcinoma. Cancer Gene Therapy (2009) 16, 832-840; doi: 10.1038/cgt.2009.21; published online 10 April 2009